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Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane protein initially identified in nonmetastatic melanomas and has been associated with human heart failure; however, its role in cardiac injury and function remains unclear. Here we show that GPNMB expression is elevated in failing human and mouse hearts after myocardial infarction (MI). Lineage tracing and bone-marrow transplantation reveal that bone-marrow-derived macrophages are the main source of GPNMB in injured hearts. Using genetic loss-of-function models, we demonstrate that GPNMB deficiency leads to increased mortality, cardiac rupture and rapid post-MI left ventricular dysfunction. Conversely, increasing circulating GPNMB levels through viral delivery improves heart function after MI. Single-cell transcriptomics show that GPNMB enhances myocyte contraction and reduces fibroblast activation. Additionally, we identified GPR39 as a receptor for circulating GPNMB, with its absence negating the beneficial effects. These findings highlight a pivotal role of macrophage-derived GPNMBs in post-MI cardiac repair through GPR39 signaling.

BACKGROUND: Aging-associated left ventricular dysfunction promotes cardiopulmonary fibrogenic remodeling, Group 2 pulmonary hypertension (PH), and right ventricular failure. At the time of diagnosis, cardiac function has declined, and cardiopulmonary fibrosis has often developed. Here, we sought to develop a molecular positron emission tomography (PET)-magnetic resonance imaging (MRI) protocol to detect both cardiopulmonary fibrosis and fibrotic disease activity in a left ventricular dysfunction model. METHODS AND RESULTS: Left ventricular dysfunction was induced by transverse aortic constriction (TAC) in 6-month-old senescence-accelerated prone mice, a subset of mice that received sham surgery. Three weeks after surgery, mice underwent simultaneous PET-MRI at 4.7 T. Collagen-targeted PET and fibrogenesis magnetic resonance (MR) probes were intravenously administered. PET signal was computed as myocardium- or lung-to-muscle ratio. Percent signal intensity increase and Δ lung-to-muscle ratio were computed from the pre-/postinjection magnetic resonance images. Elevated allysine in the heart (P=0.02) and lungs (P=0.17) of TAC mice corresponded to an increase in myocardial magnetic resonance imaging percent signal intensity increase (P

BACKGROUND: Abnormal diastolic function is an independent predictor of adverse postoperative outcomes. Mitral annular tissue Doppler velocity (e) is a key parameter for assessing diastolic function. The purpose of this study was to confirm that an acute increase in preload did not significantly impact the intraoperative measurement of e and secondarily evaluate the impact of this acute intravascular volume increase on the clinical assessment of diastolic function using a previously described simplified algorithm. METHODS: This was a prospective, non-randomized study in adult patients undergoing elective cardiac surgeries requiring transesophageal echocardiographic monitoring, arterial pressure and Swan-Ganz catheter placements as part of the surgical procedure. Following baseline echocardiographic and hemodynamic measurements, 500 ml of crystalloid solution was infused over 10 min. Hemodynamic and echocardiographic measurements were repeated 5 min after fluid administration. RESULTS: Complete data sets were available from 84 of the 100 patients who were enrolled in this study. There was no significant change in the values of e. The average baseline was 7.8 ± 2.0 cm/s (95%CI: 7.4, 8.2) and 8.1 ± 2.4 (95%CI: 7.6, 8.6) following the fluid bolus (p = 0.10). All hemodynamic variables associated with increased intravascular volume (central venous pressure, pulmonary arterial pressures and stroke volume variation) changed significantly. The overall distribution of diastolic function grades did not change following fluid administration (p = 0.69). However, there were many individual patient differences. When using this simplified algorithm, functional grading changed in 35 patients. Thirty of these 35 changes were only a single grade shift. 22 patients had worse functional grading after fluid administration while 13 had improved grading. Nine patients with normal diastolic function at baseline demonstrated diastolic dysfunction after fluid administration while 6 patients with baseline dysfunction normalized following the fluid bolus. CONCLUSION: We confirmed that e is a robust measurement that is reproducible in the intraoperative setting despite variable vascular volume loading conditions, however, the clinical assessment of diastolic function was still altered in 42% of the patients following an intravenous fluid bolus.

Background: To date, the clinical implications of the long-lasting non-alcoholic fatty liver disease (NAFLD) such as the left ventricular diastolic dysfunction (LVDD) in the course of type 2 diabetes mellitus (T2DM) are yet to be determined. The main aim of this study was to investigate the correlation between NAFLD and early LVDD progression along with demographic characteristics. Methods: This cross-sectional study was performed on ninety consecutive diabetic outpatients referred to the endocrinology clinic. Demographic data were collected using a designed checklist. Ultrasound imaging was performed to assess the fatty liver condition. To assess LV diastolic function, echocardiography was performed, using a trans-thoracic tissue Doppler echocardiography. Results: The results showed that the majority of participants were females (61.1%). The fasting blood glucose (FBG, mg/dl) level was 174.65 ±51.1. Also, the mean body mass index (BMI) was 28.92±4.19, which was significantly associated with NAFLD. It has been also estimated that 76.7% and 81.1% of diabetic patients had NAFLD and simultaneous LVDD, respectively. However, the statistical results did not show a significant association between non-progressive NAFLD and LVDD (p<0.05). Conclusion: There was no correlation between NAFLD and LVDD progression. However, timely evaluation of LVDD in T2DM outpatients with NAFLD can strongly help to prevent possible cardiomyopathy in high-risk populations. [ABSTRACT FROM AUTHOR]

Background: The relationship between diastolic function parameters and the severity of coronary artery disease (CAD) is controversial. This study aimed to determine the relationship between left ventricular diastolic function and the severity of CAD. Methods: This cross-sectional study included 63 patients with Ischemic heart disease (IHD) or those suspected of having IHD, who underwent angiography. The study was conducted in Shafa Hospital, Kerman, Iran, from 2021 to 2022. Two-dimensional (2D) strain echocardiography was used to assess left ventricular (LV) function parameters, followed by coronary angiography. Based on the severity of the disease, patients with significant CAD were placed in the case group, and patients with insignificant CAD were placed in the control group. The correlation between the CAD severity and the severity of LV diastolic dysfunction was computed. Descriptive tests, independent t tests, and Spearman correlation coefficients were used. P<0.05 was considered statistically significant. Results: The results indicated that there was no correlation between E/e' (P=0.103), left atrial volume index (LAVI) (P=0.168), tricuspid regurgitation velocity (TRV) (P=0.217), myocardial performance index (MPI) (P=0.106), E wave deceleration time (dt) (P=0.644), and late diastolic strain rate (P=0.502) with CAD severity based on SYNTAX score. However, there was a correlation between left atrial (LA) strain (P=0.017), global longitudinal strain (GLS) (P<0.001), early diastolic strain rate (P<0.001), and systolic strain rate (P=0.047) with SYNTAX score. Besides, there was a correlation between LA strain (P=0.017), GLS (P<0.001), early diastolic strain rate (P<0.001), and late diastolic strain rate (P=0.035) with numbers of epicardial coronary arteries with significant lesions. Conclusion: In contrast with 2D strain echocardiography, this study showed that conventional echocardiography parameters had no significant relationship with CAD severity. GLS had the strongest correlation with CAD severity, and diastolic strain rates had a weaker correlation with CAD severity. [ABSTRACT FROM AUTHOR]

Cirrhotic cardiomyopathy is defined as systolic and diastolic dysfunction in patients with cirrhosis, in the absence of any primary heart disease. These changes are mainly due to the malfunction or abnormalities of cardiomyocytes. Similar to non-cirrhotic heart failure, cardiomyocytes in cirrhotic cardiomyopathy demonstrate a variety of abnormalities: from the cell membrane to the cytosol and nucleus. At the cell membrane level, biophysical plasma membrane fluidity, and membrane-bound receptors such as the beta-adrenergic, muscarinic and cannabinoid receptors are abnormal either functionally or structurally. Other changes include ion channels such as L-type calcium channels, potassium channels, and sodium transporters. In the cytosol, calcium release and uptake processes are dysfunctional and the myofilaments such as myosin heavy chain and titin, are either functionally abnormal or have structural alterations. Like the fibrotic liver, the heart in cirrhosis also shows fibrotic changes such as a collagen isoform switch from more compliant collagen III to stiffer collagen I which also impacts diastolic function. Other abnormalities include the secondary messenger cyclic adenosine monophosphate, cyclic guanosine monophosphate, and their downstream effectors such as protein kinase A and G-proteins. Finally, other changes such as excessive apoptosis of cardiomyocytes also play a critical role in the pathogenesis of cirrhotic cardiomyopathy. The present review aims to summarize these changes and review their critical role in the pathogenesis of cirrhotic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Macrophages in atherosclerosis and myocardial infarction have diverse functions, such as foam cell formation and the induction of an inflammatory response that promotes ventricular dysfunction in the heart. Exosomes are small vesicles released by many different types of cells, such as macrophages, dendritic cells, platelets and other immunoregulatory cells, that facilitate communication with other cells, modulating the biological functions of recipient cells. Exosomes offer a novel therapeutic approach for the polarization of macrophages involved in cardiovascular diseases. In this review, we provide an overview of the biological role of macrophages in atherosclerosis and myocardial infarction and the effects of exosomes on these cells as therapeutic agents in the disease. [ABSTRACT FROM AUTHOR]

Background and Aim: This study explored the correlation between vitamin D status and the severity of coronary artery disease (CAD), as well as left ventricular function in patients with acute coronary syndrome (ACS). Materials and Methods: This prospective observational study included 102 patients diagnosed with ACS admitted to an Indian tertiary care facility from January 2021 to December 2021. Upon admission, the researchers collected baseline data of the patients and measured serum vitamin D levels. CAD severity was evaluated using Gensini and SYNTAX scores, and left ventricular ejection fraction (LVEF) was measured using echocardiography. Results: The study cohort had a median age of 56.5 years, with males comprising 62.7% of the total patient population. Anterior wall myocardial infarction was the most common presentation (59.8%), and 32.4% of patients had double vessel disease (DVD). The median vitamin D level was 18.3 ng/mL (interquartile range 12.7-26.8). Patients with vitamin D deficiency (≤20 ng/mL) exhibited significantly higher Gensini (46.5-94) and SYNTAX (7.5-38) scores than those with optimal levels (>30 ng/mL) (P < 0.001). A notable inverse correlation was found between vitamin D levels and both Gensini (r=-0.572, P < 0.001) and SYNTAX (r=-0.787, P < 0.001) scores. Reduced vitamin D levels were linked to decreased LVEF (P = 0.018) and a higher incidence of multivessel disease, particularly DVD (P = 0.009). Conclusion: This study revealed a significant negative correlation between low vitamin D status, CAD severity, and left ventricular dysfunction in patients with ACS. These results suggest that low vitamin D status indicates vitamin D deficiency and plays a crucial role in the occurrence and progression of coronary atherosclerosis. [ABSTRACT FROM AUTHOR]

Adiponectin (ApN) is a hormone with potent effects on various tissues. We previously demonstrated its ability to counteract Duchenne muscular dystrophy (DMD), a severe muscle disorder. However, its therapeutic use is limited. AdipoRon, an orally active ApN mimic, offers a promising alternative. While cardiomyopathy is the primary cause of mortality in DMD, the effects of ApN or AdipoRon on dystrophic hearts have not been investigated. Our recent findings demonstrated the significant protective effects of AdipoRon on dystrophic skeletal muscle. In this study, we investigated whether AdipoRon effects could be extended to dystrophic hearts. As cardiomyopathy develops late in mdx mice (DMD mouse model), 14-month-old mdx mice were orally treated for two months with AdipoRon at a dose of 50 mg/kg/day and then compared with untreated mdx and wild-type (WT) controls. Echocardiography revealed cardiac dysfunction and ventricular hypertrophy in mdx mice, which were fully reversed in AdipoRon-treated mice. AdipoRon also reduced markers of cardiac inflammation, oxidative stress, hypertrophy, and fibrosis while enhancing mitochondrial biogenesis via ApN receptor-1 and CAMKK2/AMPK pathways. Remarkably, treated mice also showed improved skeletal muscle strength and endurance. By offering protection to both cardiac and skeletal muscles, AdipoRon holds potential as a comprehensive therapeutic strategy for better managing DMD. [ABSTRACT FROM AUTHOR]

Simple Summary: Increasing number of hematopoietic stem cell transplantation (HSCT) and prolonged survival rates of these patients lead to the increase of cancer therapy-related dysfunction (CRTCD) as well. The study aimed to determine the prevalence of subclinical CTRCD in HSCT patients 12 months after HSCT and to assess the impact of clinical factors on the development of CTRCD. The study involved 55 patients who had undergone either autologous or allogeneic HSCT. Echocardiography scans were performed to check the patients' cardiac function before the transplant and again 12 months after. The study revealed that asymptomatic CTRCD was found in 27.3% of the patients 12 months after HSCT. The BEAM chemotherapy conditioning protocol following prior anthracycline use were identified as factors contributing to the development of CTRCD, therefore, these patients should undergo closer follow-up and start cardioprotective treatment when indicated. Background: Hematopoietic stem cell transplantation (HSCT) is a potentially curative procedure that is used in various hematological malignancies. However, among an increasing number of HSCT, the amount of cancer therapy-related cardiac dysfunction (CTRCD) is increasing as well. This study aimed to determine the prevalence of subclinical CTRCD in HSCT patients 12 months after HSCT and to assess the impact of clinical factors on the development of CTRCD. Material and Methods: We included 55 patients who underwent autologous or allogeneic HSCT. The patients were assessed using an echocardiography method before and 12 months after a HSCT procedure. Results: Our study revealed that during the 12-month follow-up period, asymptomatic CTRCD was observed in 15 patients (27.3%), 6 experienced moderate CTRCD, and 9 experienced mild CTRCD. Patients with previous use of anthracyclines tended to have CTRCD more often: nine patients (60%) in the CTRCD group and nine patients (22.5%) in non-CTRCD group. Patients who received the BEAM regimen for conditioning also experienced CTRCD more often: five patients (33.3%) in CTRCD group vs. two patients (5%) in the non-CTRCD group. Conclusions: Our study showed that asymptomatic CTRCD was found in 27.3% of the patients 12 months after HSCT. The BEAM chemotherapy conditioning protocol following prior anthracycline use were identified as factors contributing to the development of CTRCD. [ABSTRACT FROM AUTHOR]